Nucleotide sequence and expression of human chromosome 21-encoded superoxide dismutase mRNA.

Abstract

Cytoplasmic superoxide dismutase (SOD-1; EC 1.15.1.1) is encoded by human chromosome 21. The SOD-1 gene locus is located at chromosomal region 21q22, which is involved in Down''s syndrome. c[complementary]DNA clones containing sequences of human SOD-1 were previously isolated. Here, the nucleotide sequence of 1 clone, designated p861-10, was determined. It contains 459 nucleotides representing the entire coding region and 95 nucleotides of the 3'' untranslated region. In human cells 2 poly(A)-containing SOD-1 RNA of 0.7 and 0.5 kilobases were detected. These 2 spp. are also present in monkey cells; mouse cells contain only a 0.5-kilobase RNA. In a mouse/human hybrid line that contains chromosome 21 as the only human chromosome, the 2 human SOD-1 RNA were detected, indicating that both are encoded by this chromosome. These RNA were found in poly(A)-containing polysomal RNA and were translated in vitro to SOD-1 polypeptide; they are therefore functional mRNA. In normal human fibroblasts 0.002-0.006% of the poly(A)-containing RNA was SOD-1 RNA. The level in monosomic 21 cells was 70% of this value and the level in fibroblasts from Down''s syndrome patients was about 2 times higher than normal.